title: Paradoxically high resistance of natural killer T (NKT) cell-deficient mice to Legionella pneumophila: another aspect of NKT cells for modulation of host responses.
abstract: In the present study, we examined the roles of natural killer T (NKT) cells in host defence against Legionella pneumophila in a mouse model. The survival rate of NKT cell-deficient Jalpha281 knock-out (KO) mice was significantly higher than that of wild-type mice. There was no bacterial overgrowth in the lungs, but Jalpha281 KO mice showed enhanced pulmonary clearance at a later stage of infection, compared with their wild-type counterparts. The severity of lung injury in L. pneumophila-infected Jalpha281 KO mice was less, as indicated by lung permeability measurements, such as lung weight and bronchoalveolar lavage fluid albumin concentration. Recruitment of inflammatory cells in the lungs was approximately twofold greater in Jalpha281 KO mice on day 3. Interestingly, higher values of interleukin (IL)-1beta and IL-18, and increased caspase-1 activity were noted in the lungs of Jalpha281 KO mice from an early time point (6 h). Exogenous alpha-galactosylceramide, a ligand of NKT cells, induced IL-12 and gamma interferon at 6 h, but suppressed IL-1beta at later time points in wild-type, whereas no effects were evident in Jalpha281 KO mice, as expected. Systemic administration of heat-killed L. pneumophila, but not Escherichia coli LPS, reproduced exaggerated production of IL-1beta in the lungs of Jalpha281 KO mice. These results demonstrate that NKT cells play a role in host defence against L. pneumophila, which is characterized by enhanced lung injury and decreased accumulation of inflammatory cells in the lungs. The regulation of IL-1beta, IL-18 and caspase-1 may be associated with the modulating effect of host responses by NKT cells.
authors.affiliation: Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Microbiology and Infectious Diseases, Toho University, School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University, School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University, School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Etsu T
authors.initials: ET
authors.lastname: Fuse
authors.affiliation: Department of Microbiology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.affiliation: Department of Pathology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kaku
authors.affiliation: Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0360, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University, School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005699:Galactosylceramides / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D053148:Caspase 3; D020170:Caspase 1